Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development

Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better?

OBJECTIVE: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. METHODS: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media–intima junction or in the media. RESULTS: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age <50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of <0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples ⩾0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). CONCLUSIONS: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis

Crystalline Ultrastructures, Inflammatory Elements, and Neoangiogenesis Are Present in Inconspicuous Aortic Valve Tissue

Morbidity from calcific aortic valve disease (CAVD) is increasing. Recent studies suggest early reversible changes involving inflammation and neoangiogenesis. We hypothesized that microcalcifications, chemokines, and growth factors are present in unaffected regions of calcific aortic valves. We studied aortic valves from 4 patients with CAVD and from 1 control, using immunohistochemistry, scanning electron microscopy, and infrared spectrography. We revealed clusters of capillary neovessels in calcified (ECC), to a lesser extent in noncalcified (ECN) areas. Endothelial cells proved constant expression of SDF-1 in ECC, ECN, and endothelial cells from valvular surface (ECS). Its receptor CXCR4 was expressed in ECC. IL-6 expression correlated with CXCR4 staining and presence of lymphocytes. VEGF was expressed by ECS, its receptor by ECC and ECN. Crystalline ultrastructures were found on the surface of histologically noncalcified areas (HNCAs), spectrography revealed calcium hydroxylapatite. Our results demonstrate that crystalline ultrastructures are present in HNCAs, undergoing neoangiogenesis in an inflammatory context. These alterations could be an early witness of disease and an opening to therapy

Topographie, composition et analyse à l’échelle nanoscopique des plaques de Randall débutantes

International audienceAlexander Randall a identifié dans les années 1930 des dépôts de phosphate de calcium à la pointe des papilles rénales comme étant à l’origine des calculs rénaux oxalocalciques : les plaques de Randall. Huit décennies plus tard, nous observons à un nombre croissant de calculs générés à partir de ces plaques. Nous avons considéré que l’analyse de plaques « débutantes » pourrait permettre de déterminer leur origine

Rituximab associated vasculitis flare: incidence, predictors and outcome

International audienceTo report the incidence, predictor, and outcome of rituximab-associated autoimmune disease flare.METHODS: We conducted a retrospective study in a tertiary referral centre from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease, within 4 weeks following rituximab.RESULTS: Among the 185 patients, we identified 7 (3.4%) disease flares. All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 [2; 16] days following rituximab infusion and included acute kidney insufficiency (n=7), purpura (n=7), gastrointestinal tract involvement (n=4), and myocarditis (n=1). Patients with rituximab-associated cryoglobulinemia vasculitis flare had more frequently renal involvement (p=0.008), B cell-lymphoproliferation (p=0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p=0.004) and lower level of C4 level (0.02 vs 0.05, p=0.023) as compared to patients without flare after rituximab (n=43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after rituximab as compared to their negative counterpart [43% (95% CI: 18-100) vs 97% (95% CI: 92-100), p<0.001]. Immunofluorescence analysis of kidney biopsy in patients with rituximab associated vasculitis worsening highlighted the presence of rituximab, IgM, and IgG1 positive staining of endomembranous deposits and thrombi within kidney lesions.CONCLUSION: Rituximab-associated involves cryoglobulinemia vasculitis and is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and rituximab

Long-term clinical outcome and HAVCR2 mutations in 70 patients with subcutaneous panniculitis-like T-cell lymphoma: a study from the French Cutaneous Lymphoma Group

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